UCSF Vascular Symposium 204 Aggressive assessment and management - - PowerPoint PPT Presentation

4/5/2014 1

UCSF Vascular Symposium 204

Aggressive assessment and management are the keys to healing

Peter J. Pappas, M.D Professor of Surgery Chariman, Department of Surgery The Brooklyn Hospital

Venous Hypertension Secondary to Reflux

Leukocytes with TGF-ß1 Granules Leukocyte Diapedesis

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TGF-ß1 Release TGF-ß1 Release

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TGF-ß1 stimulated fibroblasts differentiate into myofibroblasts.

Injury Stimulus causes cytokine release And RAS activation with possible Senescence development and MMP Synthesis RAS Activation RAS Activation Normal wound healing process

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Impaired venous ulcer healing process

Treatment Options for Venous Ulcers And Levels of Evidence

• Compression Therapy
• Vein Surgery

– Superficial – Deep – Perforator

• Skin Grafting

Compression modalities

Unna Boot Multi layer Bandage

Circaid Compression Stocking

Compression Rx: Evidence of Efficacy

• Cochrane library review

– Meta-analysis

• Reviewed over 200 studies of Rx of VSU
• Conclusions

– Overall dataset is relatively poor – Appears clear that compression is better than no compression in healing VSU – Sustained compression of high strength is better than non-sustained compression

4/5/2014 5 Recent Trials of Compression Methods

Primary author Journal ref

# pts

% healed group A % healed group B

P val

Nelson J Vasc Surg 2007;45:134 245; 4 layer vs single layer 67% 4 layer at 24 wks 49% single layer at 24 wks .009 Nelson Br J Surg 2004 91:1292 387; 4 layer vs short str 92 days median for 4 layer 126 days median for SS < .05 Partsch Vasa 2001;30:108 112; 4 layer vs short str 62% 4 layer at 16 wks 73% SS at 16 wks NS Franks Wound Rep Regen 2004;12:157 156; 4 layer vs SS 69% 4 layer at 24 wks 73% SS at 24 wks NS Polignano J Wd Care 2004;13:21 68; 4 layer vs Unna 74% 4 layer at 24 wks 66% Unna at 24 wks NS

Percent healed at: 6 weeks 29% 10 weeks 57% 16 weeks 75% 52 weeks 93% 1 amputation required (0.4%)

Weeks of Treatment

10 20 30 40 50 60 70 80 90 100 4 8 12 16 20 24 28 32 36 40 44 48 52 56

Healing Rate for 252 Ulcers: UNC experience

J Vasc Surg Sept 1999

Weeks of Treatment

Percent healed at 10 weeks

• f Rx:

< 5 cm2 77% 5 to 20 cm2 61% > 20 cm2 22% All curves significant difference (P < .01) 10 20 30 40 50 60 70 80 90 100 2 6 10 14 18 22 26 34 42 52

< 5 cm2 n = 91 5 - 20 cm2 n = 94 > 20 cm2 n = 67

Healing Rate by Initial Ulcer Size

Compression and Compliance

Mayberry et al. Surgery 1991; 81:575-58

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Wrong Diagnosis: Venous Mimics

• Basal or squamous cell

carcinoma.

• Rheumatoid, lupus,

scleroderma and other collagen vascular disorders.

• Tuberculosis and syphilis.
• Pyoderma gangrenosum.
• AIDS.
• Arteriovenous

malformations.

• Cryoglobulinemia and

macroglobulinemia.

• Burns and insect bites.

Level of Evidence for Venous Ulcer Surgery Versus Compression

Summation Data for Studies Prior to 2000

Howard et al. The role of superficial venous surgery in the management of Venous ulcers: A systematic review. Eur J Vasc Endovasc Surg. 2008;36: 458-465.

Randomized Clinical Trials For Venous Ulcer Surgery

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C5-6 Disease - The ESCHAR Trial

Barwell JR, Lancet 2004

• Prospective randomized trial

– High ligation, stripping, phlebectomy and Compression versus – Multilayer compression bandaging

• 500 patients with CEAP 5 and 6 disease

– Isolated superficial reflux - 300 (60%) – Mixed superficial / deep reflux - 200 (40%)

• Endpoints

– 24 week ulcer healing – 12 month ulcer recurrence

Barwell et al. Eschar Trial. Lancet 2004; 363: 1854-1859

ESCHAR Trial - Ulcer Healing

Barwell JR, Lancet 2004

• 24 week ulcer healing - 65% in both groups

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 3 6 9 12 Months % Healed

Surgery Compression

ESCHAR Trial - Ulcer Recurrence

Barwell JR, Lancet 2004

• 12 month freedom from

recurrence (p < 0.0001) – Surgery + Compression - 12% – Compression alone

• 28%
• Four year freedom from

Recurrence (p<0.01) – Surgery + compression 31% – Compression alone

56%

0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 3 6 9 12 Months Freedom from Recurrence

Surgery Compression

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Ulcer Healing With Surgery

24 weeks

Gloviczki et al. J Vasc Surg 1999;29:489-502.

Effect Of Outflow Obstruction On Ulcer Healing: NASEPS Registry Data

Gloviczki et al. J Vasc Surg 1999;29:489-502.

Recurrence Rate With Outflow Obstruction: NASEPS Registry Data

Gloviczki et al. J Vasc Surg 1999;29:489-502.

Inadequate Surgical Correction

• LSV not ligated flush at

saphenofemoral junction.

• LSV tributaries left intact.
• LSV ligated and not
• stripped. Recurrence at

thigh due to Hunterian perforator.

• Pelvic vein varicosity.
• Neovascularization.

Stonebridge et al. Br J Surg 1995; 82: 60-62.

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Calf Muscle Pump Dysfunction

• Always consider calf muscle

pump dysfunction in patients with venous ulcer and no evidence of reflux on duplex examination.

• Important cause of pump

dysfunction is poor ankle range of motion.

• Role of physical therapy?

Back et al. J Vasc Surg, 1995;22:519-523.

Clinical Trials Data For Varicose Veins, Not Ulcer Healing: Stripping and compression versus Endovenous Technologies

CEAP Class 2 and 3 Disease: Primary Varicose Veins

History of Venous Surgery

• Trendelenburg (1890) GSV ligation upper/mid 1/3
• Homans (1916) - Flush Saphenofemoral ligation
• Mayo (1906) - Extraluminal stripper
• Babcock (1907) - Rigid intraluminal stripper
• Myers (1947) - Flexible intraluminal stripper
• 2006 - Endovenous Ablation (Laser / RF)

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Mechanism of Action Randomized Controlled Trials

• RF versus Surgery

Rautio 2002 Lurie 2005 Hinchcliff 2006 Stötter 2006

• Laser versus Surgery

de Medeiros 2005 Rasmussen 2007 Kalteis 2008 Ogawa 2008 Darwood 2008

• RF versus Laser

Morrison 2005 Almeida 2008 Goode 2008

• Varisolve Foam vs

Surgery/Sclero Wright 2006 * Foam sclero combined with sapheno-femoral ligation vs surgery Bountouroglou 2006, 2008

Stripping vs Endovenous RF Ablation

Lurie et al, J Vasc Surg 2003 Eur J Vasc Endovasc Surg 2005

• Prospective, multicenter randomized trial

Stripping n = 36 RF Ablation n = 44 p Ablation @ 1 wk 100% 90.5% Ablation @ 2 yrs 100% 92% Return to nl activity 3.89 days 1.15 days .02 Return to work 12.4 days 4.7 days < .05 Global QOL @ 1 wk + 3.7

• 9.2

.001 Global QOL @ 4 mo NS

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Evolves Trial

Venous Clinical Severity Scores

Eur J Vasc Endovasc Surg 2005

Global Quality of Life Scores

Eur J Vasc Endovasc Surg 2005

QoL scores: Immediate and Long-Term

Eur J Vasc Endovasc Surg 2005

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Rasmussen et al; J Vasc Surg 2007

• Randomized trial of

– High ligation & stripping (HL/S) - 68 legs – Endovenous laser (EVL) - 69 legs

• Office based procedures

– U/S guided tumescent anesthesia – Simultaneous miniphlebectomy

• Treatment failure at 6 months

– HL/S - 2 – EVL - 3

Stripping vs Endovenous Laser Ablation

Rasmussen et al; J Vasc Surg 2007 7.7 7.6 12 3.948 6.9 7 12.9 4.347 2 4 6 8 10 12 14 Normal Activity Work Pain Medication Cost X 1000 (euro)

HL/S EVL

No significant difference in VCSS, AVVSS, or SF-36 at 3 months p < 0.05

What Endovenous Critics Ignore

Rasmussen et al; J Vasc Surg 2007

• Highly selected population

– 1135 patients screened – 121 (11%) patients enrolled

• Office-based stripping is not standard in North America
• Although QoL not different at 3 months, early reduction of bodily

pain is important to the patient

• Return to work longer than in other series

– Cost benefit of € 312 based upon return to work in 7 days – Costs equivalent at return to work of 5.2 days

REACTIV Trial

Michaels et al, Heath Technol Assess 2006

• 246 patients extensive vv and saphenous reflux randomized to

– Conservative measures (n = 122) – Saphenous stripping / phlebectomy (n = 124)

• HRQoL (SF-6D) at 1 yr significantly better with surgery
• Fewer symptoms at 1 year with surgery

0% 10% 20% 30% 40% 50% 60% 70% 80% 90%

Aching Heaviness Itching Swelling Cosmesis

Symptoms Improved or Absent Conservative Surgery

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The Economics of Venous Ablation

4.7 12.4 7 7.6 20 14 4 17 8.9 11.5 2 4 6 8 10 12 14 16 18 20 Return to Work (Days) Lurie Rasmussen Kalteis Darwood Weighted Average

Endovenous Stripping

• Return to work variable with
• Healthcare system
• Social expectations
• Adjunct procedures (high ligation, phlebectomy)

Cost-Effectiveness of Surgery

Ratcliffe et al; Br J Surg 2006

• Randomized trial of conservative tx vs surgery
• 24 mo cost effectiveness of £4682 per QALY gained
• Below NHS threshold of £20,000 per QALY

Conservative Surgery Mean Difference Mean NHS Cost £344.53 £733.10 £388.57 AUC SF-6D 1.42 1.50 0.083 ICER *

£4682

* Incremental cost effectiveness ratio

Results of Valvular Repair Techniques

Kistner, Surgical Management of Venous Disease, ed Raju, Villavicencio, 1997

Combined Arterial And Venous Insufficiency

• Treiman et al. studied patients with combined arterial and

venous disease*. – Group 1:

• Patent arterial graft, venous stripping for superficial

reflux, no DVT.

• 95% of ulcers healed

– Group 2:

• Patent arterial graft, superficial and deep venous

reflux, no DVT.

• Four ulcers healed, three remained unhealed.

Treiman et al. J Vasc Surg 2001;33:1158-1164.

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Combined Arterial And Venous Insufficiency

• Group 3: Patent arterial graft and prior

proximal DVT. – 41% healed their ulcers, 36% remained unhealed and 13% required BKA.

• Group 4: Occluded arterial grafts

– 0% ulcer healing.

Future Directions Bioengineered Skin Bioengineered Skin

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Biofilm

Diagnosis and Treatment Algorithm For Poor Ulcer Healing

Hemodynamic Assessment Correct arterial Insufficiency Control Local wound environment Infection Compression Revascularization Followed by Venous surgery Arterial Insufficiency Ligation Stripping SEPS Valve Repair Endovascular Corrective Surgery Compression Physical Therapy Calf pump Dysfunction Other Causes APG Reflux +/- Obstruction Imaging Duplex Venography Venous Hemodynamic Assessment Recurrent Disease History and Physical

yes no yes no

Conclusions

• Surgery for Venous ulcers heals ulcers at same

rate as compression but is better at preventing recurrences.

• Endovenous ablation appears better than stripping

in terms of pain and QoL.

• Registry data provides useful information that

hasn’t been addressed in clinical trials: AVR

Conclusions

• High Venous Ulcer recurrence rates, despite best

medical care indicates an enormous need for better wound care products. – Smart dermal substitutes. – Smart stockings that provide clinicians information.

• Computer chips that can be interrogated.
• Compliance chips.

– Better therapies for wound colonization.